Studied by 3 people
animal viral replication
Share the same 5 stages as lytic bacteria
There are some changes because many animal viruses are enveloped
There are some differences between DNA and RNA viruses
Attachment
Animal viruses do not have tail fibers. Instead they use glycoprotein spikes to attach to host cells
Entry and Uncoating
There are three methods for viruses to enter animal cells
Direct Penetration – done by some naked viruses
Has correct type of spike proteins to bind with receptors
Can inject genome into the cell
Membrane fusion – phospholipid of the viral envelope fused with host cell
Because they are enveloped, they can bind onto the cell
Endocytosis – when the virus trigger receptors on the cell surface to engulf the entire virion
Triggers macrophages to eat it because it is not recognized by the cell
Virus infects the cell that engulfs it
Happens with HIV (macrophages, helper cells, lymphocytes)
bacteriophage vs animal virus
Bacteriophages inject DNA into the host cell, whereas animal viruses enter by endocytosis or membrane fusion
dsDNA synthesis
Similar to replication of normal cellular DNA and translation or proteins
Replication usually happens in the nucleus
ssDNA synthesis
Animal cells do not use ssDNA
When a ssDNA virus enters a cell, the host will synthesize a complementary strand of DNA to viral genome
Then replication and protein synthesis will proceed
+ssRNA
Ribosomes of the host cell directly translate proteins using the codons of these types of viruses
Codes for proteins allowing the viruses to remake its capsid
Essentially the +ssRNA viruses as a mRNA recognized by the cell
Makes a complimentary strand of –ssRNA
Then if it keeps making copies of negative sense of RNA then it can continue to propagate
poliovirus is a common example
+ssRNA (retrovirus) synthesis
Do not use their genome as mRNA
Instead they use reverse transcriptase to create a new strand of cDNA the cell will then use
The newly made DNA serves as a template to make more of the retrovirus and as the template for genome of the virus
HIV is the most well-known retrovirus
-ssRNA synthesis
Host ribosomes cannot translate a -RNA strand
A positive sense strand looks exactly like mRNA
Negative sense are just opposite direction
These viruses carry RNA dependent RNA transcriptase in their capsids
The enzyme then creates +RNA strands which can serve as mRNA for creating more of the virus’ genomes as well as proteins
A very common disease is influenza
dsRNA synthesis
the +RNA strand can act directly as mRNA
The -RNA strand can be transcribed into +RNA and then translated
Certain rotaviruses have this type of genome which causes gastroenteritis
lysis
the breakdown of a cell caused by damage to its plasma (outer) membrane
budding
many enveloped viruses incorporate phospholipid membranes from their host cells as they are released
phage lysogeny
can cause the phenotype of the bacterium to change from harmless into pathogenic
how cells can become cancerous
Viruses are thought to cause some 20-25% of human cancers
The most well-known is cervical cancer caused by HPV (Human Papilloma Virus)
Protooncogenes – are genes in a host cell involved in normal cell division.
Two Hit hypothesis
a virus inserts a promotor that converts a protooncogene into an oncogene
Often this first hit doesn’t cause cancer, but if a second hit damages the downstream repressor gene, \n then the oncogene disrupts cell division and causes cancer
ethical and practical difficulties to overcome in culturing viruses
Using live organisms create ethical difficulties
Cell cultures are costly
plaque assay
Look to see if virus eats through it
To estimate phage numbers, you assume that each plaque corresponds to a single phage in the original bacterium/virus mixture
prion diseases
Bovine Spongiform Encephalopathy (BSE)
Chronic Wasting Disease (CWD)
in deer and elk
vCJD – variant Creutzfeldt Jacob Syndrome
in humans
Scrapie
Kuru
prions
Proteinaceous infectious particles
In human prion diseases a normal PrP protein’s structure becomes altered and begins to affect other \n PrP proteins around it
As more of the altered PrP proteins aggregate it causes neurons to die and leave holes in the brain
Diseases caused by prions are called spongiform encephalopathies
Ingestion of injected tissue, transplants of infected tissue or contact between infected tissues and \n mucous membranes can transmit prion diseases
control and get rid of prions
in animals they kill the entire herd
They are not removed through normal autoclaving or decontamination processes
Sustained heat for several hours at extremely high temperatures (900°F and above) will reliably destroy a prion
4 types of symbiosis
mutualism
commensalism
amensalism
parasitism
commensalism
The microbe benefits without affecting the host – many types of gut bacteria
These may be mutual and we just haven’t figured it out yet
mutualism
Both host and microbe benefit from the interaction
The relationship is beneficial to both, but not necessary
amensalism
When one symbiont is harmed a second symbiont, while the second is neither harmed or helped by the first
E.g. – Pencillum fungus makes the antibiotic penicillin which inhibits nearby bacteria, but the bacteria have no effect on the fungus
parasitism
The parasite gets benefit from the host while causing it harm or disease
Any parasite that causes disease is called a pathogen
Which type of parasites would be most effective?
ones that keep host alive
microbiome
Human microbiome/normal flora/microbiota
Strep is a large member of the upper respiratory tract
Most of the fungal members are candida
Candida albicans has colonized pretty much everyone
Doesn’t really cause any issues unless the pH changes or immunocompromised
upper digestive tract microbiome
Oral cavity
Streptococcus
Lactobacillus
Probiotic yogurts
Treponema
Spirochetes
Palladium – syphilis
lower digestive tract microbiome
Small intestine
Lactobacillus
Enterococcus
Large intestine
Dense and diverse microbial population
Klebsiella
Enterococcus
Fecal coliforms
female reproductive tract microbiome
Primarily vaginal canal
Lactobacillus
Staphylococcus
Streptococcus
Candida
Babies born vaginally are colonized with other microorganisms that those delivered by caesaria
skin microbiome
Primarily populated with gram positive organisms
Staphylococcus
Streptococcus
Corynebacterium
Propionibacterium
resident microbiota
Most are commensals
transient microbiota
Things we pick up from environment around us and other people
Found in same places as resident bacteria
Until dislodged by competition
Discovered by immune system
If causing disease immune system will pick it up
Best way to get rid of them is washing hands
acquisition of microbiome
Begins at birth
Axenic environment – completely free of bacteria
Moms' womb
Initially colonized when we pass through the birth canal
Breastfeeding introduces bacteria that will become gut bacteria
conditions that cause normal flora to be pathogenic
introduction of normal microbiota into an unusual site in the body
E coli introduced from the digestive tract into the urethra can cause UTIs
Immune Suppression
Anything that suppresses the normal immune response of our body
Post surgery/injury
Steroids work to hurt the injury cascade
Why c. diff. Is common
Changes in the normal microbiome
Normal microbiota provide a competitive environment for incoming pathogens
antibiotics can allow transients to get a foothold
Stressful conditions
Emotional or Physicals stressors can allow pathogens to have a competitive advantage
Can allow pathogens to get a competitive advantage
Cold sores, candida
3 types of reservoirs
Animals
Zoonoses
Hard to eradicate because there are so many ways in which we interact with animals (food,
waste processing, pets, etc.)
Human Carriers
Can be asymptomatic for years
Typhoid Mary
Nonliving Reservoirs
Soil, water, food
contamination
The presence of microbes in the body
Can have no effect
They can become part of our normal flora.
Remain as transients for a time
Become pathogens
infection
When the pathogen overwhelms the body’s defenses
Some infections do not cause disease
portals of entry
skin
mucous membrane
MAIN PORTAL OF ENTRY
placenta parenteral route
skin portal of entry
Stratum corneum helps prevent many infections, but only as long as it remains intact
Other pathogens can enter through natural openings: hair follicles, sweat glands
Anything that opens the skin can lead to infection
Sweat glands, oil glands
mucous membrane portal of entry
MAIN PORTAL OF ENTRY
The epithelial lined body cavities that are open to the environment
This is the major portal for most microbe entry
GI tract, Respiratory, Urinary, Reproductive and the conjunctiva
The most common portal is the respiratory system
List some pathogens that enter via the respiratory route below
placenta portal of entry
Only a few types of pathogens can directly cross the placenta
In the small percentage that do, there can be severe consequences to the embryo, fetus, or mom
E.g. – If measles is able to cross the placenta it can cause fatal encephalitis in the fetus
parenteral portal of entry
This is not a traditional route of entry, but a way in which pathogens are deposited directly into tissues
needle sticks, thorns or stepping on rusty nails
Cut in the skin
adhesion factors
Viruses and bacteria most commonly use lipoprotein or glycoprotein ligands that allow them to \n attach to receptors on the host cells
The specific interaction of adhesions to their host cells often determines which types of hosts they \n can infect
Some pathogens only have one type, others can have multiple
Some are able to change their adhesions over time to evade the host’s immune system
If a virus or bacteria loses the ability to make a specific adhesion protein it will become avirulent
biofilm facilitating contamination and infection
many organisms only cause disease when they are in biofilm form
Some bacteria will change their phenotype drastically when in a biofilm
infection
When a pathogen invades a host
disease
When the injury caused by the pathogen is significant enough to interfere with normal functioning of the host
morbidity
the condition of suffering from a disease or medical condition
pathogenicity
the ability to cause disease
virulence
the degree of pathogenicity and is enhanced by virulence factors
symptoms
More subjective
Pain
Nausea
Headache
Sore throat
Fatigue
Itching, cramps etc.
signs
Objective signs of disease that are measurable
Swelling
Rash or redness
Vomiting
Diarrhea
Fever
Recommended treatment is above 100.5
Increase or decrease in WBC’s
Increase or decrease in HR
Increase or decrease in BP
syndromes
A group of signs and symptoms that characterize a disease
AIDS – hallmarks are malaise, decrease in T4 cells, diarrhea, weight loss, pneumonia, other rare
Fungal infections and cancers
asymptomatic
Lack observable signs or symptoms
May still be detected by proper testing
Some types of herpes virus infections are asymptomatic
Person may be able to transmit disease to others
etiology
The cause for a disease
Some conditions are named for the disease and not the specific pathogen
koch’s postulates
the gold standard for determining infectious disease
The suspected agent must be present in every case of the disease
The agent is isolated and grown in pure culture
The cultured agent must cause disease when inoculated into healthy host
The same agent should be found in the diseased host
Must be followed in order. – E.g., Haemophilus influenzae
koch’s postulates limitations
Some pathogens cannot be grown in lab
Some diseases are caused by a combination of pathogens
Some are polymicrobial
Combination of pathogens working together
Like some are only infectious when they form biofilms
It is unethical to test human diseases using Koch’s postulates
Some diseases are named for what they affect rather than a specific pathogen
virulence factors
extracellular enzymes
endotoxins
exotoxins
things that block phagocytosis
extracellular enzymes + virulence
Hyaluronidase – destroys hyaluronic acid, a key substance in ground substances of CT
Collagenase – destroys collagen allowing bacteria to spread.
Coagulase – causes blood clotting (coagulase test)
Staph aureus and strep are known to do this
Clots protect the bacteria
Kinases (Streptokinase, Staphylokinase) – digest blood clots and release bacteria
Allows them to spread through the body
endotoxins + virulence
Only produced by gram negative cells
The lipid A component of a gram-negative cell wall
Most common
Released when cells die
endCan cause fever, hemorrhage, inflammation
Released when the cells die or are destroyed by the host
Can cause – fever, inflammation, diarrhea, hemorrhage, shock, coagulation
exotoxins + virulence
can be produced by gram negative and positive bacteria
produced and released by the bacteria
Cytotoxins
Kill cell membranes
Neurotoxins
Nervous tissue
Botulinum
Damages synaptic transmission (nerve to nerve and nerve to muscle)
Enterotoxins
GI tract
Our bodies can produce antibodies that will neutralize exotoxins before they make us sick
Vaccines that look for exotoxins are looking for a certain protein signature
endotoxins vs exotoxins
Exotoxins are more serious than endotoxins, but if a large number of gram-negative cells die then endotoxins can cause disease
Need smaller number of exotoxins to cause disease
Onset of disease from exotoxin is more rapid and severe right off the bat
For endotoxins they take longer to cause disease
infectious disease stages
incubation period
prodromal phase
illness period (climax)
decline
convalescence
You can be infectious at any stage
antiphagocytic factors + chemicals
Capsules – are composed of the same things as body cells
Can evade detection for longer
Some capsules also make the bacteria very slippery and had to grab
Antiphagocytic Chemicals – chemicals produced by bacteria that prevent lysosomes in the phagocytes from attaching to the bacteria and allows them to survive inside the phagocytes
E.g. – M factor produced by Strep pyogenes
incubation period
the time between entry of the microbe and symptom appearance
Many infectious agents this is between 1-7 days
Depends on virulence of microorganism and infective dose
State and health of host (faster infection if immunocompromised)
Site of infection
prodromal phase
a time of mild signs or symptoms
Mild signs and symptoms
Some infectious diseases that can skip the prodromal phase (GI bugs)
illness phase
known as climax
when signs and symptoms are most intense
Most severe part
When you feel the worst
The hosts immune system has not responded adequately yet or it is completely overwhelmed
Often but not always the most infective stage
decline phase
As signs and symptoms subside
Immune system starts to recover or when antibiotics or antiviral meds kick in
When fever goes away but still sick
convalescence phase
The body systems return
Length depends upon same factors that cause disease (no co-morbidities)
vehicle transmission
Airborne
When it is small enough to be picked up in air currents
Much more common occurrence with dental and surgical drills
Waterborne
Can act as a reservoir as well
Fecal-oral route
Foodborne
Another fecal-oral route
From improper food handling
Bodily fluids
Considered underneath water transmission
Can be a form of direct contact
Blood or semen come in contact with open cut
Should always be treated as if they contain pathogens
vector
Biological
Bites
Insects
Mosquito is most common
Mechanical
Indirect transmission
e.g., fly walks on sandwich
contact transmission
Direct
Bodily contact
Touching, kissing, sex,
Biting or scratching in zoonoses
Vertical transmission
Mom passes it to the baby via placentas
Indirect
Fomites – inanimate objects that are capable of transferring pathogens
e.g., toothbrush, medical equipment, money
Droplet
Droplets of mucous propelled out of nose or throat when talking, sneezing, coughing
Most travel 1m or less
droplet vs airborne transmission
Distance
Aerosols/airborne remain suspended in the air
classifications of infectious diseases
By taxonomic group
By body system affected
Longevity and Severity
acute diseases
Symptoms develop rapidly and runs its course quickly
e.g., influenza, rotavirus, strep throat
chronic diseases
Disease with usually mild symptoms that develop slowly and a long time
e.g., COPD (Chronic Obstructive Pulmonary Disease), cancer, mono
subacute disease
Disease whose time course and symptoms range between acute and chronic
e.g., COVID
latent disease
disease that appears a long time after infection
e.g., Proin diseases, Cold sores
local infection
infection only in a specific area of the body
e.g., Tick bite
communicable disease
Able to be transmitted from one host to another
noncommunicable disease
disease not passed from person to person
contagious disease
communicable disease that is easily spread
epidemiology
The study where, when, and how diseases occur
How diseases affect the population
Can be applied to chronic diseases not just acute
incidence rate
number of new cases that are appearing in a specific time
Better for ongoing outbreak
prevalence rate
the total number of cases appearing in a specific time
Better for the burden of disease
endemic
naturally occurring in a population/normally around
Common cold
sporadic
few cases of diseases that pop up
Can be related or unrelated
epidemic
large new emergence of disease in an area
More cases than normally predicted for a given region
Continued or sustained spread of disease
Different than outbreak
Outbreaks are limited
Not enough momentum or population to keep the outbreak going
Outbreak of food poisoning
pandemic
worldwide epidemic
epidemiological approaches
Descriptive
Early studies
Trying to figure out what the cause it
What the reservoirs are
Index case – person who is the original host or reservoir
Analytical
Used to try to find associations between risk factors and behavior patterns of disease
Often retrospective studies (after the fact)
Experimental
Highest level of epidemiological studies
Hypothesis generating and testing experimental studies based upon previous information
healthcare associated diseases
Types of HAIs
Exogenous – picked up in a healthcare setting
Endogenous – opportunists because of treatment
Iatrogenic – caused by things like catheters, surgery, wrong antibiotics
Handwashing protocols can reduce infection by more than 50%
factors affecting HAIs
Presence of microbes in the hospital setting
Immunocompromised patients
Transmission of pathogens between staff, and patients
specific immune response
adaptive
Humoral – B-cell mediated
Cell based – T-cell mediated
nonspecific immune response
innate
Mechanical
Cells
Chemicals
Inflammation
Major component of immune response
Does not know the difference between sprain or bacteria
mechanical barriers
keep pathogens out
Skin
Secretions
Oils on skin
Sweat
Tears
Saliva
Mucosa
cells
complement
Made of about 20 proteins that are activated when exposed to bacterial antigens
For generalized bacterial infections
Series of proteins found in our blood
Some are part of the hemoglobin molecule
Classical Pathway
Stimulation by antigen-antibody complex
Alternate Pathway
Stimulation by microorganism cell wall
Literally pokes a hole in the wall of pathogens
interferon
Part of non-specific immune response
Generalized viral infections
Infected cell (host 1) will die, but interferon will cause neighboring cells to produce protective anti-viral protein coats
IFN’s used to treat some forms of Herpes and Hepatitis
Also used for autoimmune disorders
MS
Cells can produce interferon
Moves to neighboring cells and telling it to protect themselves
toll like receptors
Integral proteins found on the cell membrane of phagocytes
Trigger your body’s responses to a number of various bacterial and viral pathogens
There are 10 different TLR’s found on human phagocytes
Binding of Pathogen Associated Molecular Patterns (PAMP) triggers infected cells to do things \n like: apoptosis, initiate the inflammatory mechanism, or stimulate the adaptive response
neutrophils
phagocytes – about 126 billion/day produced
Usually the first WBC to make it to an infection
1 time use (like a honeybee stinger)
Pus =dead neutrophils, microbes, pathogens
macrophages
monocytes in blood, macrophages in tissue
Leave blood and increase numbers at site of infection
They are the cleanup crew
Include many different types – dendritic cells, microglia, alveolar, hepatic
basophils
mobile
Release factors which attract more WBC’s (chemotactic factors)
mast cells
nonmobile
Are found near sites of possible pathogen influx
Release chemotaxic factors
Can also phagocytose bacteria
eosinophils
Act as moderators of inflammatory response and kill parasites by releasing enzymes all over them
Note
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